RaNA Therapeutics Presents Data Supporting Gene Upregulation as Spinal Muscular Atrophy Treatment

RaNA Therapeutics recently released preclinical data on its gene upregulation technology, which selectively triggers gene expression within cells, as a treatment for spinal muscular atrophy (SMA). The data were given in a poster presentation at the recent Keystone Symposium for Chromatin and Epigenetics in British Columbia, Canada.

SMA, a major cause of infant mortality, results from mutations or deletions of SMN1 gene that encodes the protein SMN, important for the survival of motor neurons. SMN2 can compensate for SMN1 if its expression can be activated to produce functional protein. According to a press release, RaNA’s gene upregulation technology increased expression of the SMN protein  in preclinical models.

Titled “A gene upregulation technology that selectively activates genes by targeting PRC2-associated lncRNA,” the presentation addressed findings that a long non-coding RNA (lncRNA) recruits a gene-repressive complex (PRC2) to SMN2, ultimately leading in its repression. The use of a proprietary short oligonucleotide, however, prevented PRC2 from being recruited to SMN2. Data showed this resulted in increased SMN mRNA and protein levels in the cells of SMA patients.

“These data are exciting, as they pre-clinically validate our scientific approach to selectively upregulating gene expression to increase protein levels in the body for therapeutic benefit,” said Ron Renaud, chief executive officer for RaNA Therapeutics. “SMA is a devastating disease, and we are focused on rigorously exploring and advancing our oligonucleotide technology to develop treatment options that make a meaningful difference to patients.”

Other results of RaNA’s oligonucleotide technology presented include:

• Observation of sustained duration of action by oligonucleotides with comprehensive bioavailability
• Analysis of the genome after oligonucleotide therapy revealed highly specific activity
• Single molecule RNA-FISH data indicated that the lncRNA functions in cis and that a treatment based in oligonucleotide does not disrupt localization of lncRNA, and is further evidence of its specificity

Balkrishen Bhat, PhD, RaNA’s vice president of Chemistry, will present these and other findings at the HealthTech’s Oligonucleotide Therapeutics and Delivery Conference on April 5, 2016, in Cambridge, Massachusetts. Dr. Bhat will also introduce in vitro and in vivo proof of concept of the company’s mRNA stabilization platform to enhance the half-life and upregulation of mRNA and protein.

SMA affects about 1 in every 6,000 to 10,000 people. Its primary symptom is loss of motor function, likely caused by early motor neuron loss.